Tumor-targeting and redox dual-responsive hyaluronic acid-based polymeric micelles loaded with celastrol for breast cancer treatment

Hyaluronic acid derivatives have broad prospects in the in vivo targeted delivery of insoluble antitumor drugs. In this study, rhein-selenocystamine-hyaluronic acid (RSeHA) polymeric micelles (PMs) were designed and developed to load celastrol (Cela) to solve its poor water solubility, low bioavailability, and severe toxicity for breast cancer treatment. Cela-loaded RSeHA PMs (Cela/RSeHA PMs) with a particle size of 159.61 ± 8.33 nm and drug-loading capacity of 36.57 ± 1.66 % showed excellent redox dual-responsiveness for drug rapid-release in tumors. Cela/RSeHA PMs can be taken up by the MCF-7 and 4T1 cells, exhibiting a good killing effect on these cells in a time- and concentration-dependent manner. Pharmacokinetic results showed that Cela/RSeHA PMs significantly enhanced the bioavailability and prolonged the circulation time of Cela in vivo . The PMs enhanced Cela's distribution in the tumor, improving its tumor-targeting ability. The pharmacodynamic results in 4 T1 tumor-bearing mice showed that Cela/RSeHA PMs could inhibit the growth of tumors, with a tumor inhibition rate of 59.45 ± 12.64 %, and significantly decrease serum CA15–3 level, displaying a good anti-breast cancer effect without organ damage. In summary, RSeHA PMs are expected for tumor-targeting and redox dual-responsive delivery of water-insoluble anti-breast cancer drugs.